Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
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| MTBC0 PGAP re-annotation | GTP-binding protein |
|---|
| Revised (this work) | CobW/P47K-family nucleotide- and metal-binding protein (Pfam cobW PF02492 + CobW_C PF07683), of the COG0523 subfamily of putative metallochaperones (often involved in zinc/cobalt homeostasis). The specific metal and role are not established. |
|---|
Curated reference (UniProt)
| UniProt |
P9WPI5
SwissProt · reviewed
· Evidence at protein level
|
|---|
| UniProt name | Zinc chaperone Rv0106 |
|---|
| EC (curated) |
EC 3.6.5.-
|
|---|
| Curated function | Zinc chaperone that directly transfers zinc cofactor to target proteins, thereby activating them. Zinc is transferred from the CXCC motif in the GTPase domain to the zinc binding site in target proteins in a process requiring GTP hydrolysis. |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | cobalamin synthesis CobW domain protein |
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| Orthologous group | COG0523 |
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Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are
computed annotations, not manual curation; cross-check against the primary literature
before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS |
0.958 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
3 synonymous, 8 missense, 0 nonsense, 0 frameshift
|
|---|
pN/pS from segregating SNPs (singletons removed) normalised by possible sites.
Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene).
A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic
variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A
clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a
convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
cobW | PF02492.26 |
2.4e-08 | 54–174 |
CobW/HypB/UreG, nucleotide-binding domain |
CobW_C | PF07683.20 |
6.2e-13 | 238–351 |
Cobalamin synthesis protein cobW C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
rpmB1 (50S ribosomal protein L28),
medium confidence from genomic context alone
(score 656 excluding text-mining).
This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv2056c rpsN2 |
30S ribosomal protein S14 |
931 |
906 |
coexpression:849 |
Rv2058c rpmB2 |
50S ribosomal protein L28 |
932 |
853 |
coexpression:801 textmining:560 |
Rv2057c rpmG1 |
50S ribosomal protein L33 |
844 |
825 |
coexpression:703 |
Rv2059 hyp |
hypothetical protein |
978 |
820 |
coexpression:805 textmining:887 |
Rv0280 PPE3 |
PPE family protein PPE3 |
888 |
804 |
coexpression:804 textmining:457 |
Rv2990c hyp |
hypothetical protein |
950 |
757 |
coexpression:757 textmining:803 |
Rv2055c rpsR2 |
30S ribosomal protein S18 |
882 |
736 |
coexpression:703 textmining:574 |
Rv0105c rpmB1 |
50S ribosomal protein L28 |
779 |
656 ctx |
neighborhood:594 |
Rv2861c mapB |
methionine aminopeptidase |
497 |
477 |
experimental:474 |
Rv0734 mapA |
methionine aminopeptidase |
494 |
474 |
experimental:474 |
Rv0979A rpmF |
50S ribosomal protein L32 |
492 |
474 |
|
Rv3525c |
siderophore-binding protein |
488 |
459 |
coexpression:415 |
Rv1381 pyrC |
dihydroorotase |
477 |
458 |
coexpression:414 |
Rv2062c cobN |
cobalamin biosynthesis protein CobN |
578 |
449 |
coexpression:404 |
Rv3575c |
LacI family transcriptional regulator |
437 |
438 |
|
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression,
experimental, database, text-mining) into a 0–1000 score. The ctx
badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion,
phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an
unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not
depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with
the operon context and the primary literature before assigning a function.
Evidence
- MTBC0 PGAP product: 'GTP-binding protein'
- Pfam: cobW PF02492 (E=2.4e-08), CobW_C PF07683 (E=6.2e-13) -- COG0523 putative metallochaperone
ESM Atlas signal (exploratory)
Ancestral protein hash a54b5715ebe2c0e1edfbe14c2ddf8629 ·
10 ESM-space neighbours (max similarity 0.883).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 16165 |
1.23 |
Accessory C-terminal substrate lids |
| 2 | 1243 |
1.17 |
P-loop NTPase Walker A/B |
| 3 | 12948 |
1.03 |
Phosphate binding switch loops |
| 4 | 12425 |
0.91 |
C-terminal effector domains of NTPases |
| 5 | 11158 |
0.80 |
N-terminal membrane anchoring modules |
| 6 | 10020 |
0.75 |
NTPase switch loops |
| 7 | 9490 |
0.73 |
N-terminal RNA-binding IDRs |
| 8 | 3167 |
0.68 |
N-terminal phosphate-binding loop |
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024),
An imputed ancestral reference genome for the MTBC,
doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_214620.1)
- Domains: Pfam-A via hmmscan --cut_ga — cobW (PF02492.26), CobW_C (PF07683.20)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0523
- Curated reference: UniProt
P9WPI5
(SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of
145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
34 functional partner(s); context anchor
rpmB1
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000116|Rv0106|
MRTPVILVAGQDHTDEVTGALLRRTGTVVVEHRFDGHVVRRMTATLSRGELITTEDALEFAHGCVSCTIRDDLLVLLRRLHRRDNVGRIVVHLAPWLEPQPICWAIDHVRVCVGHGYPDGPAALDVRVAAVVTCVDCVRWLPQSLGEDELPDGRTVAQVTVGQAEFADLLVLTHPEPVAVAVLRRLAPRARITGGVDRVELALAHLDDNSRRGRTDTPHTPLLAGLPPLAADGEVAIVEFSARRPFHPQRLHAAVDLLLDGVVRTRGRLWLANRPDQVMWLESAGGGLRVASAGKWLAAMAASEVAYVDLERRLFADLMWVYPFGDRHTAMTVLVCGADPTDIVNALNAALLSDDEMASPQRWQSYVDPFGDWHDDPCHEMPDAAGEFSAHRNSGESR
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